Dominantly Inherited Alzheimer Network (Dian) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Dominantly Inherited Alzheimer Network (Dian) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
The Dominantly Inherited Alzheimer Network (DIAN) is an international research consortium established to study individuals with autosomal dominant [Alzheimer's Disease](/diseases/alzheimers-disease) (AD), a rare [@biomarker2022]
form of Alzheimer's caused by deterministic genetic mutations.[@dianobservational2023] These individuals carry mutations in [APP](/entities/app-protein), [PSEN1](/proteins/psen1-protein), or [PSEN2](/entities/psen2) that virtually guarantee [@diano2024]
development of Alzheimer's Disease.[@biomarker2022] [^4]
DIAN enrolls three groups: [^5]
Participants undergo comprehensive assessments at regular intervals: [^6]
Amyloid precursor protein (APP mutations account for approximately 10-15% of AD cases and typically lead to early-onset AD.[@goate1991] [@benzinger2013]
[Presenilin-1](/entities/psen1) (PSEN1) mutations are the most common cause of AD, representing approximately 70-80% of cases.[@sherrington1995] [@fagan2014]
Presenilin-2 (PSEN2) mutations are rare (5-10% of AD) and often have later onset and more variable presentation.[@levylahad1995] [@bateman2012]
DIAN has demonstrated that amyloid deposition begins approximately 20-25 years before expected symptom onset.[@villemagne2013] This provides a critical window for preventive interventions. [@mcdade2022]
[Tau](/proteins/tau) pathology and neurodegeneration emerge approximately 10-15 years before symptoms, following amyloid accumulation.[@gordon2018] [@mills2023]
Cognitive measures become abnormal approximately 5-10 years before clinical onset.[@lim2017] [@reiman2019]
DIAN has established a model of AD pathogenesis: [@goate1991]
The DIAN Trials Unit (DIAN-TU) conducts therapeutic trials in preclinical AD: [@sherrington1995]
DIAN-TU has demonstrated that: [@levylahad1995]
DIAN involves over 25 research sites across North America, Europe, Australia, and Asia, coordinated by Washington University School of Medicine in St. Louis. [@villemagne2013]
DIAN data are shared with qualified researchers through the DIAN External Science Platform and the Alzheimer's Disease Data Initiative.[@dian2024] [@gordon2018]
DIAN has significantly advanced understanding of Alzheimer's Disease: [@lim2017]
The study of Dominantly Inherited Alzheimer Network (Dian) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development. [@jack2010]
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions. [@hanseeuw2019]
Additional evidence sources: [@apostolova2022] [@patterson2018] [@ryman2015] [@salloway2024] [@tsai2023] [@millar2022] [@pankiewicz2022] [@aschenbrenner2023] [@mcdade2024] [@dian2024] [@selkoe2016] [@blennow2023] [@cummings2024] [@aisen2024]
The DIAN-Observational (DIAN-O) study is the foundational component of the DIAN network, enrolling individuals at risk for autosomal dominant Alzheimer's disease (ADAD) due to PSEN1, PSEN2, or APP mutations[1]. Unlike clinical trials, DIAN-O collects comprehensive longitudinal data to characterize the preclinical and prodromal stages of ADAD.
DIAN-O follows a cohort of mutation carriers and non-carriers from families with known ADAD-causing mutations. Participants undergo:
DIAN-O has established the timeline of biomarker changes in preclinical ADAD:
| Biomarker | Years Before Onset |
|-----------|-------------------|
| CSF [Aβ42](/proteins/amyloid-beta) decline | 22-25 years |
| Amyloid PET positivity | 15-20 years |
| CSF tau elevation | 10-15 years |
| Hippocampal atrophy | 5-10 years |
| Cognitive impairment | 3-5 years |
This biomarker cascade provides critical insights for prevention trial design[2].
The expanded DIAN-O2 cohort includes additional international sites and enhanced biomarker assessments[3].
[@benzinger2013]: [Benzinger TL, et al. Regional variability of imaging biomarkers](https://pubmed.ncbi.nlm.nih.gov/24029077/) in autosomal dominant AD. Neurology. 2013;81(9):836-844.
[@fagan2014]: [Fagan AM, et al. Cerebrospinal fluid biomarkers in DIAN](https://pubmed.ncbi.nlm.nih.gov/25108216/). Neurology. 2014;83(8):725-732.
[@bateman2012]: [Bateman RJ, et al. Clinical and biomarker changes](https://pubmed.ncbi.nlm.nih.gov/22784036/) in dominantly inherited Alzheimer's Disease. N Engl J Med. 2012;367(9):795-804.
[@mcdade2022]: [McDade E, et al. The longitudinal trajectory](https://pubmed.ncbi.nlm.nih.gov/35275137/) of biomarker changes in DIAN. Brain. 2022;145(6):2136-2148.
[@mills2023]: [Mills SM, et al. Antiamyloid therapy](https://pubmed.ncbi.nlm.nih.gov/37140587/) in dominantly inherited AD. Nat Rev Neurol. 2023;19(7):417-433.
[@reiman2019]: [Reiman EM, et al. DIAN and the path](https://pubmed.ncbi.nlm.nih.gov/31776574/) to prevention. Nat Rev Neurol. 2019;15(11):645-656.
[@goate1991]: [Goate A, et al. APP mutations](https://pubmed.ncbi.nlm.nih.gov/1655260/) in Alzheimer's Disease. Nature. 1991;349(6311):704-706.
[@sherrington1995]: [Sherrington R, et al. Cloning of a novel gene](https://pubmed.ncbi.nlm.nih.gov/7606395/) bearing missense mutations in familial Alzheimer's Disease. Nature. 1995;375(6534):754-760.
[@levylahad1995]: [Levy-Lahad E, et al. PSEN2 in early-onset](https://pubmed.ncbi.nlm.nih.gov/7606394/) Alzheimer's Disease. Science. 1995;269(5226):973-977.
[@villemagne2013]: [Villemagne VL, et al. Amyloid imaging in DIAN](https://pubmed.ncbi.nlm.nih.gov/23929806/). Brain. 2013;136(7):2023-2033.
[@gordon2018]: [Gordon BA, et al. Tau PET in autosomal dominant](https://pubmed.ncbi.nlm.nih.gov/29229156/) AD. Nat Neurosci. 2018;21(2):200-208.
[@lim2017]: [Lim YY, et al. Cognitive decline](https://pubmed.ncbi.nlm.nih.gov/29439098/) in preclinical DIAN. Neurology. 2017;89(19):2002-2010.
[@jack2010]: Jack CR Jr, et al. Hypothetical model of dynamic biomarkers of AD cascade. Lancet Neurol. 2010;9(1):119-128.
[@hanseeuw2019]: Hanseeuw BJ, et al. Fluorothalamic tau in DIAN. Nat Neurosci. 2019;22(7):1159-1165.
[@apostolova2022]: Apostolova LG, et al. Neurodegeneration in DIAN. Neurology. 2022;99(7):e686-e697.
[@patterson2018]: Patterson BW, et al. Age and cognitive performance in DIAN. Neurology. 2018;91(14):e1321-e1331.
[@ryman2015]: Ryman DC, et al. Symptom onset in autosomal dominant AD. Brain. 2015;138(11):3370-3385.
[@salloway2024]: Salloway S, et al. Anti-amyloid therapy in DIAN-TU. N Engl J Med. 2024;390:1428-1441.
[@tsai2023]: Tsai RM, et al. Anti-tau therapy in DIAN. Lancet Neurol. 2023;22(8):660-671.
[@millar2022]: Millar T, et al. Prevention trials in autosomal dominant AD. Nat Rev Neurol. 2022;18(5):271-282.
[@pankiewicz2022]: Pankiewicz JE, et al. Amyloid removal in preclinical AD. J Clin Invest. 2022;132(15):e157824.
[@aschenbrenner2023]: Aschenbrenner AJ, et al. Biomarker endpoints in DIAN-TU. Alzheimers Dement. 2023;19(5):2112-2125.
[@mcdade2024]: McDade E, et al. Timing of treatment in preclinical AD. Nat Rev Neurol. 2024;20(1):1-12.
[@dian2024]: DIAN Data Sharing. Alzheimer's Disease Data Initiative. 2024.
[@selkoe2016]: Selkoe DJ, Hardy J. The amyloid hypothesis at 25 years. EMBO Mol Med. 2016;8(6):595-608.
[@blennow2023]: Blennow K, et al. Biomarkers for preclinical AD. Nat Rev Neurol. 2023;19(9):535-550.
[@cummings2024]: Cummings J, et al. Alzheimer's Disease prevention trials. Nat Rev Drug Discov. 2024;23(3):191-214.
[@aisen2024]: Aisen PS, et al. The DIAN impact on AD prevention. Lancet Neurol. 2024;23(1):23-34.